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Objective: to evaluate the efficacy and safety of the type I interferon (IFN) receptor inhibitor anifrolumab (AFM, Safnelo®) in patients with systemic lupus erythematosus (SLE) in real-life clinical practice over an observation period of 6 months.Material and methods. The prospective 6-month study included 21 patients with SLE fulfilling the 2012 SLICC criteria, predominantly women (n=17,81%), median age – 31 [27; 46] years, disease duration – 9 [6.0; 11.0] years. Standard laboratory values and immunological markers of SLE were examined in all patients. The SLEDAI-2K index was used to determine the activity of SLE, and the severity of the mucocutaneous syndrome was assessed using the Cutaneous Lupus Disease Area and Severity Index (CLASI) index. Organ damage was assessed using the SLICC/ACR Damage Index (DI). After 6 months, the achievement of low activity was assessed according to the Lupus Low Disease Activity State (LLDAS) indexResults and discussion. At the time of inclusion in the study, the mean SLEDAI-2K activity index for the group was 8 [6.0; 10.0] points, the median CLASI index – 8.6±8.2 points, 81% of patients had skin and mucosal lesions, 66% had non-erosive polyarthritis, and high immunological activity was observed in all cases. Various irreversible organ damage was observed in 86 of patients. The average DI was 2.2±1.5 points. At the start of AFM therapy, all patients received glucocorticoids (GCs) at a mean dose of 10.7±5.6 mg/day, 52% of patients received a dose above 10 mg/day, 76% of patients continued to take hydroxychloroquine, and 33% of patients took immunosuppressants. Significant positive dynamics were observed with AFM therapy. The average CLASI index for the group after 3 months of treatment was 1.2±4.1 points, after 6 months – 0.3±1.2 points (p

Objective: to summarize scientific information about the basic principles of modern drug therapy for patients with chronic myeloid leukemia (CML) considering their individual characteristics.Material and methods. The basis of the study included modern scientific articles and clinical guidelines on CML diagnosis and treatment (2021), State Register of Medicines (SRM) of the Russian Federation, instructions for the use of medicines. The following methods were used: structural analysis, analytical method, content analysis, retrospective analysis, systematic approach, situational-logical and graphical methods of analysis.Results. The analysis made it possible to summarize scientific information about the basic principles of drug therapy for patients suffering from CML. It was revealed that the problem of CML therapy today is relevant, since every year there is an increase in the incidence of this nosology. Currently, the most significant is the prescription of tyrosine kinase inhibitors (TKIs), since they have pronounced effects and are well tolerated by patients. Therapy for CML in TKIs prescription consists of several lines. Imatinib is the first line therapy because it has better safety profile. There are combinations with imatinib; for example, it is used together with interferon alfa, which allows, in some cases, to increase the response to treatment. The following drugs are used in the second line: nilotinib, dasatinib, bosutinib, ponatinib. If TKI therapy is ineffective, it is possible to prescribe standard chemotherapy, interferon therapy, or bone marrow transplantation in the absence of contraindications. Studies are underway on the possibility of using and including in clinical guidelines such drugs as arsenic trioxide, decitabine, omacetaxime, inhibitors of farnesyl transferases, granulocyte-macrophage factors, antitumor vaccines. The analysis of SRM identified 27 trade names for TKIs, the share of domestic drugs was 60%. There were no Russian analogues for bosutinib and ponatinib in SRM, which are recommended for use in case of ineffective TKI therapy of previous lines.Conclusion. The study of drug provision for CML patients is an urgent task for pharmaceutical practice and for the healthcare system as a whole. Currently, the acute issues are the individual approach to the treatment of each CML patient considering concomitant diseases, and the search for new, more effective drugs that can increase the life expectancy and quality of life of patients suffering from this disease.

Abstract Background ATLL (Adult T-Cell Leukemia/Lymphoma) is an aggressive hematological malignancy. This T-cell non-Hodgkin lymphoma, caused by the human T-cell leukemia virus type 1 (HTLV-1), is challenging to treat. There is no known treatment for ATLL as of yet. However, it is recommended to use Zidovudine and Interferon Alfa-based regimens (AZT/IFN), chemotherapy, and stem cell transplant. This study aims to review the outcome of patients with different subtypes of ATLL treated with Zidovudine and Interferon Alfa-based regimens. Methods A systematic search was carried out for articles evaluating outcomes of ATLL treatment by AZT/IFN agents on human subjects from January 1, 2004, until July 1, 2022. Researchers assessed all studies regarding the topic, followed by extracting the data. A random-effects model was used in the meta-analyses. Results We obtained fifteen articles on the AZT/IFN treatment of 1101 ATLL patients. The response rate of the AZT/IFN regimen yielded an OR of 67% [95% CI: 0.50; 0.80], a CR of 33% [95% CI: 0.24; 0.44], and a PR of 31% [95% CI: 0.24; 0.39] among individuals who received this regimen at any point during their treatment. Our subgroup analyses’ findings demonstrated that patients who received front-line and combined AZT/IFN therapy responded better than those who received AZT/IFN alone. It is significant to note that patients with indolent subtypes of disease had considerably higher response rates than individuals with aggressive disease. Conclusion IFN/AZT combined with chemotherapy regimens is an effective treatment for ATLL patients, and its use in the early stages of the disease may result in a greater response rate.

Some theories suggest that the development of the immune response to clear hepatitis B triggers the intestinal tissue damage seen in celiac disease in genetically predisposed individuals. Although the role of hepatitis B virus infection in the development of autoimmune diseases has been widely discussed in the literature, it remains a controversial topic. Our objective is to review whether there is an association between hepatitis B and celiac disease and the particularities of vaccination against hepatitis B in celiac patients. [ABSTRACT FROM AUTHOR]

Background: ATLL (Adult T-Cell Leukemia/Lymphoma) is an aggressive hematological malignancy. This T-cell non-Hodgkin lymphoma, caused by the human T-cell leukemia virus type 1 (HTLV-1), is challenging to treat. There is no known treatment for ATLL as of yet. However, it is recommended to use Zidovudine and Interferon Alfa-based regimens (AZT/IFN), chemotherapy, and stem cell transplant. This study aims to review the outcome of patients with different subtypes of ATLL treated with Zidovudine and Interferon Alfa-based regimens. Methods: A systematic search was carried out for articles evaluating outcomes of ATLL treatment by AZT/IFN agents on human subjects from January 1, 2004, until July 1, 2022. Researchers assessed all studies regarding the topic, followed by extracting the data. A random-effects model was used in the meta-analyses. Results: We obtained fifteen articles on the AZT/IFN treatment of 1101 ATLL patients. The response rate of the AZT/IFN regimen yielded an OR of 67% [95% CI: 0.50; 0.80], a CR of 33% [95% CI: 0.24; 0.44], and a PR of 31% [95% CI: 0.24; 0.39] among individuals who received this regimen at any point during their treatment. Our subgroup analyses' findings demonstrated that patients who received front-line and combined AZT/IFN therapy responded better than those who received AZT/IFN alone. It is significant to note that patients with indolent subtypes of disease had considerably higher response rates than individuals with aggressive disease. Conclusion: IFN/AZT combined with chemotherapy regimens is an effective treatment for ATLL patients, and its use in the early stages of the disease may result in a greater response rate. [ABSTRACT FROM AUTHOR]

Simple Summary: This was a phase III randomized controlled trial investigating the outcomes of low-dose interleukin-2 (IL-2) plus interferon alfa (IFNα) versus sunitinib as the first line and axitinib as the second line in patients with low- and intermediate-risk metastatic renal cell carcinoma (mRCC). There was a trend toward better total progression-free survival up to the end of the second line for IL-2 + IFNα but no significant advantage in terms of overall survival. The study was underpowered to draw any definitive conclusions. The results showed no clear advantage of IL-2 + IFNα over sunitinib in the first line; however, it may be an option in some relatively low-risk mRCC cases due to the difference in the adverse events profile. This trial was registered with the University Hospital Medical Information Network (UMIN), center identifier UMIN 000012522. Background: The sequence of first-line cytokine and second-line molecular targeted therapies may be suitable for some patients with metastatic renal cell carcinoma (mRCC) because of the expectation of complete remission and durable response achieved with cytokine therapy. Methods: This was a phase III randomized controlled trial investigating the outcomes of low-dose interleukin-2 (IL-2) plus interferon alfa (IFNα) versus sunitinib as the first line and axitinib as the second line in patients with low- and intermediate-risk mRCC. Results: Thirty-five patients were randomly assigned. The total progression-free survival (PFS) to the end of the second line was 29.0 months (95% CI, 11.7–46.3) in the IL-2 + IFNα group and 16.3 months (95% CI, 6.3–26.4) in the sunitinib group. The PFS hazard ratio for the IL-2 + IFNα group relative to the sunitinib group was 0.401 (95% CI, 0.121–1.328; p = 0.135). The hazard ratio for overall survival (OS) was 1.675 (95% CI, 0.418–6.705; p = 0.466), which was better in the sunitinib group than in the IL-2 + IFNα group but not statistically significant. The types of adverse events (AEs) differed significantly, although there was no significant difference in the incidence of AEs. Conclusions: There was a trend toward better total PFS for IL-2 + IFNα, but it was not significant. There was also no advantage of IL-2 + IFNα in terms of OS. The study was underpowered to draw any definitive conclusions. The results showed no clear advantage of IL-2 + IFNα over sunitinib in the first-line setting; however, it may be an option in some relatively low-risk mRCC cases due to the difference in the AE profile. This trial was registered with the University Hospital Medical Information Network (UMIN), center identifier UMIN 000012522. [ABSTRACT FROM AUTHOR]

This Phase Ib study combined programmed death-ligand 1 inhibitor, atezolizumab, with other immunomodulatory agents in locally advanced and metastatic solid tumors. Arms B-D evaluated atezolizumab plus interferon-α, with/without vascular endothelial growth factor inhibitor, bevacizumab, in renal cell carcinoma (RCC) and other solid tumors. Arm B predominantly recruited patients with previously treated RCC or melanoma to receive atezolizumab plus interferon α-2b. Arm C investigated atezolizumab plus polyethylene glycol (PEG)-interferon α-2a in previously treated RCC. Arm D evaluated atezolizumab plus PEG-interferon α-2a and bevacizumab. Primary objectives were safety and tolerability; secondary objectives included clinical activity. Combination therapy was well tolerated, with safety profiles consistent with known risks of individual agents. The most frequent treatment-related toxicities were fatigue, chills, and pyrexia. The objective response rate (ORR) in arm B was 20.0% overall and 17.8% in patients with previously treated checkpoint inhibitor–naive RCC (n = 45). No responses were reported in arm C. The highest ORR in arm D was 46.7% in patients with treatment-naive RCC (n = 15). Data showed preliminary clinical activity and acceptable tolerability of atezolizumab plus interferon α-2b in patients with previously treated checkpoint inhibitor–naive RCC and of atezolizumab plus PEG-interferon α-2a and bevacizumab in patients with treatment-naive RCC.

This Phase Ib study combined programmed death-ligand 1 inhibitor, atezolizumab, with other immunomodulatory agents in locally advanced and metastatic solid tumors. Arms B-D evaluated atezolizumab plus interferon-β, with/without vascular endothelial growth factor inhibitor, bevacizumab, in renal cell carcinoma (RCC) and other solid tumors. Arm B predominantly recruited patients with previously treated RCC or melanoma to receive atezolizumab plus interferon β-2b. Arm C investigated atezolizumab plus polyethylene glycol (PEG)-interferon β-2a in previously treated RCC. Arm D evaluated atezolizumab plus PEG-interferon β-2a and bevacizumab. Primary objectives were safety and tolerability; secondary objectives included clinical activity. Combination therapy was well tolerated, with safety profiles consistent with known risks of individual agents. The most frequent treatment-related toxicities were fatigue, chills, and pyrexia. The objective response rate (ORR) in arm B was 20.0% overall and 17.8% in patients with previously treated checkpoint inhibitor-naive RCC (n = 45). No responses were reported in arm C. The highest ORR in arm D was 46.7% in patients with treatment-naive RCC (n = 15). Data showed preliminary clinical activity and acceptable tolerability of atezolizumab plus interferon β-2b in patients with previously treated checkpoint inhibitor-naive RCC and of atezolizumab plus PEG-interferon β-2a and bevacizumab in patients with treatment-naive RCC. [ABSTRACT FROM AUTHOR]

Patients treated for adult T-Cell leukemia/lymphoma (ATL) have a poor prognosis and are prone to infectious complications which are poorly described. As the French reference center for ATL, we retrospectively analyzed 47 consecutive ATL (acute, n = 23; lymphoma, n = 14; chronic, n = 8; smoldering, n = 2) patients between 2006 and 2016 (median age 51 years, 96% Afro-Caribbean origin). The 3-year overall survival (OS) was 15.8%, 11.3%, and 85.7% for acute, lymphoma, and indolent (chronic and smoldering) forms respectively. Among aggressive subtypes, 20 patients received, as frontline therapy, high dose of zidovudine and interferon alfa (AZT-IFN⍺) resulting in an overall response rate (ORR) of 39% (complete response [CR] 33%) and 17 chemotherapy resulting of an ORR of 59% (CR 50%). Ninety-five infections occurred in 38 patients, most of whom had an acute subtype (n = 73/95; 77%). During their follow-up, patients receiving frontline chemotherapy or frontline AZT-IFNα developed infections in 74% (n = 14/19) and 89% (n = 24/27) of the cases respectively. Sixty-four (67%) of infections were microbiologically documented. Among them, invasive fungal infections (IFI, n = 11) included 2 Pneumocystis jirovecii pneumonia, 5 invasive aspergillosis, and 4 yeast fungemia. IFI exclusively occurred in patients with acute subtype mostly exposed to AZT-IFNα (n = 10/11) and experiencing prolonged (> 10 days) grade 4 neutropenia. Patients with aggressive subtype experiencing IFI had a lower OS than those who did not (median OS 5.4 months versus 18.4 months, p = 0.0048). ATL patients have a poor prognosis even in the modern era. Moreover, the high rate of infections impacts their management especially those exposed to AZT-IFNα. [ABSTRACT FROM AUTHOR]

Myeloid malignancies are a heterogeneous group of clonal haematopoietic disorders, caused by abnormalities in haematopoietic stem cells (HSCs) and myeloid progenitor cells that originate in the bone marrow niche. Each of these disorders are unique and present their own challenges with regards to treatment. Acute myeloid leukaemia (AML) is considered the most aggressive myeloid malignancy, only potentially curable with intensive cytotoxic chemotherapy with or without allogeneic haematopoietic stem cell transplantation. In comparison, patients diagnosed with chronic myeloid leukaemia (CML) and treated with tyrosine kinase inhibitors (TKIs) have a high rate of long-term survival. However, drug resistance and relapse are major issues in both these diseases. A growing body of evidence suggests that Interferons (IFNs) may be a useful therapy for myeloid malignancies, particularly in circumstances where patients are resistant to existing front-line therapies and have risk of relapse following haematopoietic stem cell transplant. IFNs are a major class of cytokines which are known to play an integral role in the non-specific immune response. IFN therapy has potential as a combination therapy in AML patients to reduce the impact of minimal residual disease on relapse. Alongside this, IFNs can potentially sensitize leukaemic cells to TKIs in resistant CML patients. There is evidence also that IFNs have a therapeutic role in myeloproliferative neoplasms (MPNs) such as polycythaemia vera (PV) and primary myelofibrosis (PMF), where they can restore polyclonality in patients. Novel formulations have improved the clinical effectiveness of IFNs. Low dose pegylated IFN formulations improve pharmacokinetics and improve patient tolerance to therapies, thereby minimizing the risk of haematological toxicities. Herein, we will discuss recent developments and the current understanding of the molecular and clinical implications of Type I IFNs for the treatment of myeloid malignancies.

Myeloid malignancies are a heterogeneous group of clonal haematopoietic disorders, caused by abnormalities in haematopoietic stem cells (HSCs) and myeloid progenitor cells that originate in the bone marrow niche. Each of these disorders are unique and present their own challenges with regards to treatment. Acute myeloid leukaemia (AML) is considered the most aggressive myeloid malignancy, only potentially curable with intensive cytotoxic chemotherapy with or without allogeneic haematopoietic stem cell transplantation. In comparison, patients diagnosed with chronic myeloid leukaemia (CML) and treated with tyrosine kinase inhibitors (TKIs) have a high rate of long-term survival. However, drug resistance and relapse are major issues in both these diseases. A growing body of evidence suggests that Interferons (IFNs) may be a useful therapy for myeloid malignancies, particularly in circumstances where patients are resistant to existing front-line therapies and have risk of relapse following haematopoietic stem cell transplant. IFNs are a major class of cytokines which are known to play an integral role in the non-specific immune response. IFN therapy has potential as a combination therapy in AML patients to reduce the impact of minimal residual disease on relapse. Alongside this, IFNs can potentially sensitize leukaemic cells to TKIs in resistant CML patients. There is evidence also that IFNs have a therapeutic role in myeloproliferative neoplasms (MPNs) such as polycythaemia vera (PV) and primary myelofibrosis (PMF), where they can restore polyclonality in patients. Novel formulations have improved the clinical effectiveness of IFNs. Low dose pegylated IFN formulations improve pharmacokinetics and improve patient tolerance to therapies, thereby minimizing the risk of haematological toxicities. Herein, we will discuss recent developments and the current understanding of the molecular and clinical implications of Type I IFNs for the treatment of myeloid malignancies. [ABSTRACT FROM AUTHOR]

Exactly 30 years ago, hepatitis C virus was identified. Over the years, tremendous success has been achieved in the treatment of hepatitis C, which is currently considered to be an almost completely curable disease. The review presents the main stages in the development of hepatitis C antiviral therapy, the efficacy of various treatment regimens. The greatest progress in treatment was noted over the past 5 years when drugs with direct antiviral action appeared and began to be widely used, including in Russia, which ensure the elimination of the virus in 90-95% of cases.

Introduction: Interferon α is a type-I interferon molecule with antiviral and antineoplastic properties. Interferon α treatment is also used in the management of uveitis and believed to have immunomodulatory properties demonstrated by increased number of regulatory T cells. The aim of this study was to define the influence of interferon α-2a treatment on monocyte subsets in patients with uveitis. Materials and Methods: Six patients with uveitis and 7 healthy control subjects were included in this study. Blood samples were obtained from the uveitis patients before treatment with interferon α-2a and at the 1st month of treatment (or at clinical remission). Peripheral blood mononuclear cells were stained with anti-CD16, anti-CD14, anti-PD-1, anti-CTLA-4, anti-LAG-3, anti-TIM-3 and anti-TIGIT antibodies and analyzed with flow cytometry. Data were analyzed with FlowJo software and statistical analysis was performed with SPSS 21.0 software. Results: Six patients with uveitis (5 Behçet’s, 1 Eales disease, mean age: 29.0±3.8 years, 4 male, 2 female) and 7 healthy control subjects (mean age: 28.4±4.9 years, 3 male, 4 female) were included. The number of CD14+CD16- classical monocytes were increased and CD16+ non-classical monocytes were decreased in patients with active uveitis compared to controls (p=0.037 and p=0.045) and this difference disappeared after treatment with interferon α-2a. There was no difference in immune checkpoint receptor expressions between groups at baseline. PD-1 expression increased significantly after interferon α-2a treatment (p=0.01). Conclusion: Interferon α-2a treatment increases the ratio of non-classical monocytes and their expression of PD-1. These changes may be associated with the previously demonstrated immunomodulatory effects of interferon α-2a in patients with uveitis. [ABSTRACT FROM AUTHOR]

The effect of IFNa-2b on the migration, proliferation, and expression of epithelial and mesenchymal markers of MCF-7 tumor adenocarcinoma cells in 2D and 3D cell cultures was examined. A significant cytostatic effect of IFNa-2b on the tumor population was detected. It was found that changes in the expression of epithelial (CKs and EpCAM) and mesenchymal markers were caused by changing the growth type of the tumor population. IFNa-2b inhibited migration of tumor cells to the suspension fraction and promoted an increase in expression of CK and EpCAM in 2D and 3D cell cultures, but only in the 3D culture was expression of vimentin increased. IFNa-2b caused an increase in CK and EpCAM expression by 50.5% and 47.8%, respectively, compared with the control in the 2D cell culture. In the 3D cell culture this increase was 33% and 34%, respectively, compared with the control. IFNa-2b stimulated the differentiation and inhibited the migrational ability of tumor cells in the early stages of breast cancer development. [ABSTRACT FROM AUTHOR]

Introducción: bexaroteno es un rexinoide aprobado en el tratamiento de estadios tempranos y avanzados del linfoma cutáneo de células T (LCCT). Caso Clínico: el presente reporte de casos mostramos los resultados del empleo de bexaroteno en dosis bajas más fototerapia o Interferon alfa 9 millones en el tratamiento del LCCT. Ocho pacientes fueron tratados, cinco fueron Micosis fungoides, dos Linfoma Epidermotrópico CD8 agresivo y uno fue un Síndrome Sézary. La respuesta global fue del 62.5% (5/8) y la duración media de respuesta fue de 20 meses. El bexaroteno en dosis bajas en combinación a fototerapia o interferon alfa 2a puede ser efectivo en el tratamiento del LCCT.

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Introduction. Until the 1990s, there was no available treatment for chronic hepatitis C, but during this decade the benefits of interferon-alfa therapy were reported. At the end of the 1990s, the pegylated interferon-alfa 2a/b has significantly altered the treatment, whereas direct acting antivirals have significantly affected the treatment. The aim of this study was to show the most significant predictive factors of therapy response among patients with chronic hepatitis C treated with pegylated interferon-alfa 2a/b and ribavirin. Material and Methods. A non-randomized retrospective study included 292 patients with chronic hepatitis C treated at the Clinic for Infectious Diseases, Clinical Center of Vojvodina, from 2008 to 2015. Results. The study showed that therapeutic response was not affected by sex, serum viral load, or if the therapy was applied for the first time or repeated. A sustained virological response was statistically significantly more frequent in younger patients, as well as in patients without extrahepatic manifestations. Cases with higher progression of fibrosis were associated with lower chance for sustained virological response. Genotype 1 showed to be a predictor of adverse response to therapy, and genotype 3 as a predictor of sustained virological response. Steatosis was significantly less frequent in patients with genotype 1 with sustained virological response. Patients with a shorter duration of infection were more prone to sustained virological response. Conclusion. A positive response to pegylated interferon-alfa 2a/b and ribavirin was found in 70.20% of patients with chronic hepatitis C. Elderly age, late detection of the infection, hepatitis C virus 1 genotype, fibrosis progression, presence of hepatic steatosis, and extrahepatic manifestations were risk factors for poor treatment outcome. [ABSTRACT FROM AUTHOR]

Background and study aims Occult hepatitis B infection (OBI) is known to be mostly prevalent in chronic hepatitis C (CHC) patients and OBI reactivation might be life-threatening in patients undergoing interferon (IFN)-free direct acting antiviral (DAA) therapy. As previous studies have revealed a relationship between OBI and non-response to IFN-based antiviral therapy, the aim of the current study was to determine if there was a higher prevalence of OBI in IFN non-responders than responders. Patients and Methods This retrospective cross-sectional study was conducted in CHC patients who had previously received IFN-based antiviral therapy. Serum samples of 100 HBsAg negative CHC patients were tested for HBV DNA, anti-HBc IgG, anti-HBs, ALT and AST. The presence of OBI was compared between 50 IFN responders and 50 IFN non-responders. Patients with a history of previous HBV infection, patients with evidence of cirrhosis and patients who had received IFN therapy within the last one year were excluded from the study. Results Anti-HBc IgG positivity was determined in 53% of the patients. HBV DNA positivity, indicating OBI was determined in 1 (1%) patient. This patient was anti-HBc IgG positive, anti-HBs negative, ALT and AST levels were normal. The HBV DNA and anti-HBc IgG positivity rates were higher in the non-responder group than in the responder group, but the difference was not statistically significant ( p  = 0.31 and p  = 0.07 respectively). Conclusion According to the results of this study, the prevalence of OBI is lower than expected amongst CHC patients in Turkey and it may not be necessary to apply routine screening to IFN non-responders for OBI infection before DAA therapy. However, there is a need for multicentre studies with larger patient series. [ABSTRACT FROM AUTHOR]

The adult T-cell lymphoma is a peripheral T-cell neoplasm caused by the human T-cell lymphotropic virus, type 1 (HTLV-1), endemic in Colombia. We present the case of a 66 years-old male patient who presented with skin lesions in trunk and extremities. The pathology study established the diagnosis of peripheral T-cell lymphoma NOS (not otherwise specified). Local management of skin lesions started, but it progressed, so adult T-cell lymphoma was suspected and confirmed. Colombia is an endemic country for HTLV-1. Dermatologists should be familiar with this malignancy and its different skin manifestations, occasionally simulating mycosis fungoides, in order to identify more cases in a timely manner. [ABSTRACT FROM AUTHOR]

Introduction: Interferon alfa (IFN-α) has been used for over 30 years to treat myeloproliferative neoplasms. Recombinant IFN-α (rIFN-α) and pegylated IFN-α (Peg-IFN-α) have been shown to provide effective therapy for essential thrombocythemia (ET) and polycythaemia vera (PV), as well as early stage primary myelofibrosis (PMF) in several clinical studies. Patients and methods: This report presents a retrospective analysis of 60 patients with MPN who were treated with rIFN-α or Peg-IFN-D outside clinical trials. Results: Retrospective stratification at diagnosis included 34 (57%) patients with PV, 5 (8%) with ET and 21 (35%) with PMF. Median age was 43 years (16-70). Median treatment duration was 107.5 months, with 11 patients treated with Peg IFN-D for a median duration of 24 months. Median follow up was 164 months. 24 patients (40%) achieved complete remission, 29 patients (48%) achieved partial remission and 7 patients (12%) failed to achieve partial remission. Toxicities were recorded in 42 patients (70%): chronic „flu-like syndrome", psychiatric toxicity, hepatotoxicity, dermatotoxicity, ocular and neurotoxicity. Thirteen (22%) patients stopped the treatment because of toxicity. Conclusion: IFN-α effectively controls disease in a significant proportion of Ph-negative MPN patients. However, its use in clinical practice has unfortunately been limited by side effects. These results support the need for further efficacy studies of IFN-α in this group of patients. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is a global public health concern with significant impacts. It primarily spreads through blood-to-blood contact, such as sharing needles among drug users. Given the wide prevalence of risk factors, HCV continues to pose a major threat. Hence, it is crucial to understand its characteristics, structure, and genotypes to prevent, treat, and potentially eradicate it. This narrative review aims to explore the history of HCV treatment, highlight the breakthroughs achieved with direct-acting antiviral (DAA) therapy, address potential barriers to HCV eradication, and discuss future treatment possibilities. For this article, relevant studies were identified using various databases, including PubMed, ClinicalTrials.gov, and Journal Storage. The literature search revealed that after identifying HCV and studying its characteristics, interferon alfa and ribavirin became primary treatment options. However, due to their limited coverage against different HCV genotypes, ethnic variations, and suboptimal sustained virological response, the development of DAAs became essential. Combining various DAAs, such as sofosbuvir and velpatasvir, for a duration of 12 weeks has become the standard HCV treatment, with effectiveness against most genotypes. Additionally, ongoing clinical trials have shown promising results for other drugs such as CDI31244/sofosbuvir/velpatasvir, sofosbuvir/coblopasvir, and daclatasvir/asunaprevir. Despite the success of DAAs and ongoing efforts to discover more effective treatments, the high costs of DAAs pose a significant challenge to eradicating HCV, as not all patients can afford these expensive therapies. Furthermore, the ability of HCV to mutate limits the potential for vaccine development. Therefore, it is crucial to focus on developing more cost-effective strategies to control the spread of HCV and create novel, highly effective, and affordable DAAs., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Bernal et al.)

Renal hücreli karsinomun çocukluk çağındaki tedavisi esas olarak geniş cerrahi rezeksiyon ile yapılmaktadır. Çoğu evre I-II vaka için radikal nefrektomi ve lenf nodu diseksiyonu yeterli olurken ileri evrelerde immünoterapinin de dahil olduğu farklı tedavi yöntemleri tanımlanmıştır. Burada tanı anında opere edilemeyen, sonrasında interferon alfa ile başarılı bir şekilde tedavi edilen ileri evre renal hücreli karsinomu olan 9 yaşında bir kız sunulmuştur.

Este artículo revisa los principales aspectos de la hepatitis C crónica (epidemiológicos y genómicos, relacionados con un mejor conocimiento molecular del ciclo vital del virus de la hepatitis C, VHC) y de modo notable la terapia estándar con interferón α pegilado y ribavirina. El énfasis se ha puesto especialmente en los aspectos biológicos de la respuesta inmunológica del hígado frente al VHC y en la valoración del grado de fibrosis hepática mediante la elastografía de transición.This article reviews the main aspects of chronic hepatitis C (epidemiological, genomic related to enhanced molecular understanding of the life cycle of the hepatitis C virus, HCV) especially standard therapy with pegilated interferon α and ribavirin. Emphasis is also placed on the immune response of the liver to HCV and the assessment of liver fibrosis via transient elastography.

Introducción: hasta hace poco, el tratamiento estándar de oro para la hepatitis C eran los interferones pegilados (Peg-IFN) en combinación con la ribavirina (RBV). Con la llegada de nuevos fármacos, se propuso evaluar los resultados del tratamiento y a los pacientes en espera de la nueva terapia. Materiales y métodos: este estudio analítico transversal evaluó el resultado del tratamiento en individuos con hepatitis C crónica, y luego comparó a individuos que tienen experiencia en no responder al tratamiento basado en interferón (IFN) con individuos sin experiencia de tratamiento previo. Resultados: el estudio incluyó 192 individuos. Entre 87 pacientes sometidos a tratamiento, se observaron bajas tasas de respuesta viral sostenida (RVS). La comparación de los 105 pacientes no tratados previamen- te y los 87 que habían recibido tratamiento con IFN previamente evidenció que entre los pacientes en espera de nuevas terapias, los individuos sin tratamiento previo presentaron mayor proporción de genotipo 1 (68% frente a 49%; p = 0,028), menores niveles de ALT (91,1 ± 73,0 frente a 126,0 ± 73,40 U/L; p = 017), de AST (70,1 ± 51,3 frente a 89,7 ± 47,40 U/L; p = 050), de GGT (85,3 ± 85,1 frente a 148,4 ± 123,9 U/L; p = 0,007) y menor proporción de fibrosis significativa (24,3 frente a 83,3; p

CONTEXT: Pharmacovigilance studies aim to detect, assess, understand and prevent risks of adverse effects of medications or any other possible drug related problem. Alpha interferon is being produced by Bio-Manguinhos/Fiocruz, Rio de Janeiro, RJ, Brazil and used in the treatment of chronic hepatitis C at Brazilian National Health System. OBJECTIVE: To study the safety profile and effectiveness of alpha interferon in a sample of Brazilian patients with chronic hepatitis C genotypes 2 and 3, in Porto Alegre, RS, Brazil. METHOD: We followed a cohort of chronic hepatitis C genotypes 2 and 3 patients treated with alpha interferon plus ribavirin in a specialized outpatient clinic in southern Brazil. Adverse events were collected and classified according to severity in monthly structured interviews. To measure effectiveness, hepatitis C viral load was evaluated before, at the end and 24 weeks after the treatment. RESULTS: We followed 141 patients during the study period, of which 52.5% were female with mean age of 52 years. The most frequent adverse events were fatigue (84%), headache (79%) and myalgia (75%). There were 13 treatment interruptions due to adverse events, 9 of those considered serious adverse events. Virological response at end of treatment was 54.6% and after 24 weeks 39.7%, considering all patients who started treatment. CONCLUSION: The product produced by Bio-Manguinhos has similar efficacy and adverse event and sustained virological response profiles comparable to those found in the literature. This is the first study of pharmacovigilance performed with the Brazilian product. These data will be useful for planning and management of this disease in Brazil.

Se estudiaron 13 pacientes con leucemia mieloide crónica y anemia hemolítica autoinmune inducida por el interferón alfa, a quienes se les realizó la detección de inmunoproteínas y la caracterización de las subclases de IgG en los hematíes mediante la prueba de antiglobulina directa (PAD) y la técnica de microplacas. Se aplicó además un ELISA para la cuantificación de inmunoglobulinas en los hematíes. Se detectó la presencia de IgG y C3 en el 53,84 % de los casos, IgG sola en el 23,07 % y en el 15,38 % se identificaron autoanticuerpos IgG e IgA. En 11 pacientes se demostró la presencia de IgG1 y en un caso se identificaron además autoanticuerpos de la subclase IgG3. El ELISA detectó autoanticuerpos en concentraciones de 183 moléculas de IgG por hematíe en un paciente con PAD negativa. En los pacientes con hemólisis de alto grado se encontró una concentración de autoanticuerpos entre 1 500 y 3 180 moléculas de IgG por hematíe, mientras que en los casos con hemólisis de bajo grado se comportó entre 183 y 1 000 moléculas. Se observó una correlación negativa entre las cifras de Hb y los valores de haptoglobina plasmática con el número de moléculas de IgG por hematíe y una correlación positiva entre este último con el conteo de reticulocitos.We studied 13 patients with chronic myeloid leukemia and autoimmune hemolytic anemia induced by interferon alfa. They underwent tests for immune protein detection and characterization of IgG subclasses in RBCs by direct antiglobulin test (PAD) and the microplate technique. Also they were applied ELISA test for quantifying immunoglobulins in the red blood cells. It was detected the presence of IgG and C3 in 53.84 % of cases, IgG alone in 23.07 % and in 15.38 % were identified IgG and IgA autoantibodies. In 11 patients the presence of IgG1 was showed and also in one case the subclass IgG3 autoantibodies was identified. The ELISA detected antibodies at concentrations of 183 IgG molecules per erythrocyte in a patient with negative PAD. In high-grade hemolysis patients, it was found a concentration of autoantibodies between 1 500 and 3 180 molecules of IgG per erythrocyte, while in low-grade hemolysis patients it behaved between 183 and 1 000 molecules. There was a negative correlation between Hb and plasma haptoglobin values with the number of IgG molecules per erythrocyte and a positive correlation between the latter with the reticulocyte count.

Interferon-alpha (IFN-alpha) is one of the main drugs used in the treatment of hepatitis C. Use of IFN-alpha has some limitations that result in poor treatment efficacy and low patient compliance. Therefore, the aim of this study was to develop poly-ε-caprolactone (PCL) microspheres containing IFN-alpha as an alternative for the treatment of chronic hepatitis C. Microspheres were prepared using the multiple emulsion followed by solvent evaporation technique. Particle size, surface morphology, drug content and encapsulation efficiency of the microspheres produced were evaluated. The stability of the formulation was assessed after 90 days at -20ºC. An in vitro release study was performed in PBS. In vitro cytotoxicity of the formulation was studied using hepatic cell line. The freeze-dried microspheres had mean particle size, IFN-alpha content, and encapsulation efficiency of 38.52 ± 4.64 µm, 15.52 ± 3.28% and 83.93 ± 5.76%, respectively. There were no significant changes during storage and the structural integrity of the protein was not compromised by the preparation technique. A total of 82% of the IFN-alpha was released after 28 days and the developed microspheres did not present cytotoxicity to the hepatic cell line. In vivo studies are currently underway to evaluate the biological activity of IFN-alpha encapsulated into microspheres.O interferon alfa (IFN-alfa) é um dos principais fármacos utilizados no tratamento de hepatite C, mas o seu uso apresenta limitações que resultam em baixa eficácia do tratamento e não adesão do paciente. Diante disso, este estudo objetiva o desenvolvimento de microesferas de poli-ε-caprolactona (PCL) contendo IFN-alfa como alternativa ao tratamento de hepatite C crônica. As microesferas foram preparadas pelo método de emulsão múltipla seguido de evaporação do solvente e caracterizadas quanto ao diâmetro médio das partículas, morfologia da superfície, taxa e eficiência de encapsulamento. A estabilidade da formulação foi acompanhada durante 90 dias a -20 ºC. O estudo de liberação in vitro foi realizado em PBS. A citotoxicidade da formulação foi avaliada utilizando linhagem de células hepáticas. As microesferas liofilizadas apresentaram diâmetro médio, taxa de encapsulamento e eficiência de encapsulamento de 38,52 ± 4,64 µm, 15,52 ± 3,28% e 83,93 ± 5,76%, respectivamente. Não foram observadas alterações significativas durante o armazenamento e a integridade estrutural da proteína foi mantida após o preparo. Oitenta e dois por cento de IFN-alfa foram liberados em 28 dias e a formulação desenvolvida não apresentou toxicidade para as células testadas. Estudos in vivo estão em andamento para avaliar a atividade biológica do IFN-alfa encapsulado nas microesferas.

Sarcoidosis is a chronic multisystemic granulomatous disease that is triggered by an autoimmune process. Nowadays, this pathology represents a well-recognized but uncommon complication for antiviral treatment in hepatitis C virus (HCV) infection. Herein, we report a remarkable case of 47-year-old woman treated for chronic HCV infection; the patient has developed interferon alfa-induced sarcoidosis involving the central nervous system. The evolution was fatal despite disrupting the antiviral therapy and initiating a high-dose corticotherapy. This complication of interferon alfa treatment was reported in the literature in only one case. Through this case and a review of the literature, we aim to underline the importance of screening for sarcoidosis before and during the follow-up of HCV patients undergoing antiviral therapy.

OBJECTIVE: To assess whether the cystic craniopharyngiomas can be controlled with the use of intratumoral applications of interferon alpha. METHOD: Nineteen patients with the diagnosis of cystic craniopharyngioma were treated with intratumoral chemotherapy with interferon alpha from January 2002 to April 2006. All patients underwent placement of an intracystic catheter connected to an Ommaya reservoir. Through this reservoir were made applications during chemotherapy cycles. Each cycle corresponded to application of 3,000,000 units of interferon alpha three times per week on alternate days totalizing 36,000,000 units. Response to treatment was evaluated by calculating the tumor volume on MRI control after one, three and six months after the end of each cycle. Patients who developed worsening of symptoms or who had insignificant reduction in tumor volume during follow-up underwent repeat cycle chemotherapy. RESULTS: Four patients received four cycles of chemotherapy, three patients received three cycles, six patients received two cycles and six patients received one. The lower percentage of reduction in tumor volume was 60% and the bigger reduction was 98.37%. Eleven patients had a reduction greater than 90%. Five patients had a tumor reduction between 75 and 90% and in three patients the tumors were reduced by less than 75%. No deaths occurred during treatment and side effects of interferon alpha were well tolerated. No treatment was discontinued. Follow-up after the last application ranged from one year and five months to three years and nine months. CONCLUSION: The intratumoral chemotherapy with interferon alpha decreases the volume of cystic craniopharyngiomas and so far can be considered a new therapeutic alternative.

Las anemias diseritropoyéticas congénitas (ADC) son un grupo de trastornos heridatarios de la hematopoyesis caracterizados por anemia refractaria de severidad variable. Se distinguen 3 tipos fundamentales: 1, 2 y 3. El gen responsable de la ADC-1 (CDAN1) se localiza en el cromosoma 15q15, aunque estudios moleculares recientes evidencian la heterogeneidad de esta enfermedad. Se presenta una paciente de 3 años con diagnóstico de ADC-1 que a los 3 meses de edad comenzó con anemia severa, hiperbilirrubinemia indirecta, reticulocitosis ligera, altos requerimientos transfusionales y alteraciones del desarrollo pondoestatural dado por baja talla. La prueba de Ham fue negativa y en sangre periférica predominó la macrocitosis. En el examen de la médula ósea se observó diseritropoyesis con hiperplasia eritroide, hematopoyesis megaloblástica, precipitados intracitoplasmáticos, núcleos irregulares, cariorrexis, binuclearidad y puentes internucleares. No hubo respuesta al tratamiento con interferón alfa recombinante. La paciente se encuentra con tratamiento quelante con deferroxamina y se ha planteado la posibilidad de un trasplante de células progenitoras hematopoyéticas alogénico no relacionado.The congenital dyserytropoietic anemias (CDT) include a series of hematopoiesis hereditary disorders characterized by a refractory anemia of variable severity. There are three fundamental types: 1, 2 and 3. The gen accounted for CDT-1(CDAN1) is located in 15q15 chromosome, although recent studies demonstrate the heterogeneity of this disease. This is the case of a female patient aged 3 diagnosed with CDT-1who at three months old had a severe anemia, indirect hyperbilirubinemia, slight reticulocytosis, high transfusion requirements and stature disorders due to its low height. Ham’s was negative and in peripheral blood there was macrocytosis predominance. Bin bone marrow examination it was possible to observe dyserytropoiesis with erythroid hyperplasia, megaloblast hematopoiesis, intracytoplasm precipitates, irregular nuclei, karyorresis, binuclearization and internuclear bridges. There wasn’t response to treatment with the recombinant type α interferon. Patient is under chelation treatment with deferoxamine and it was proposed the possibility of no-related allogenic of hematopoietic parent cell.

CONTEXTO: Tem sido sugerido que os pacientes coinfectados por vírus da hepatite C e da imunodeficiência humana (VHC/HIV) devam ser tratados com interferon peguilado associado à ribavirina (PEG+RBV) porque as taxas de resposta virológica sustentada seriam maiores do que aquelas obtidas com interferon convencional associado à ribavirina (IFN+RBV). No entanto, há escassez de trabalhos na literatura comparando as duas opções de tratamento nesta população de pacientes, em especial fora do cenário de ensaios clínicos. OBJETIVO: Avaliar a resposta virológica sustentada ao tratamento com IFN+RBV versus PEG+RBV em pacientes coinfectados pelo vírus da hepatite C genótipo 1 e vírus da imunodeficiência humana (VHC-1/HIV), no âmbito do programa do Ministério da Saúde. MÉTODOS: Trata-se de estudo de coorte misto, onde foram revisados prontuários de pacientes coinfectados por VHC-1/HIV tratados com IFN+RBV (antes de 2002) ou PEG+RBV (a partir de 2002) pelo período de 48 semanas, no âmbito da Secretaria da Saúde do Estado do Rio Grande do Sul. Foram avaliadas as características demográficas (idade, gênero e peso), contagem de células CD4 e histopatologia - atividade inflamatória (A) e fibrose - segundo classificação METAVIR. O nível de significância adotado na análise estatística foi de 5%. RESULTADOS: Foram avaliados 81 pacientes coinfectados por VHC-1/HIV, 22 que utilizaram IFN+RBV e 59 que utilizaram PEG+RBV por 48 semanas. Os grupos eram semelhantes no que tange à média de idade, gênero, peso, contagem de células CD4 e grau de fibrose. Os pacientes que utilizaram IFN+RBV apresentaram maior atividade histológica com proporção de A2+A3 que superava aqueles que utilizaram PEG+RBV (PCONTEXT: It has been suggested that coinfected patients HCV/HIV must be treated with pegylated interferon associated to ribavirin (PEG+RBV), because of better taxes of sustained virological response when compared to those treated with conventional interferon associated to ribavirin (IFN+RBV). There are few studies in the literature comparing these two treatments options in this population. OBJECTIVE: To evaluate the sustained virological response to the treatment with IFN+RBV versus PEG+RBV in coinfected patients HCV/HIV genotype 1, in a public health program. METHODS: It is a cohort study, where the data of the coinfected patients treated with IFN+RBV (before 2002) or PEG+RBV (from 2002) during 48 weeks in the Brazilian Health Ministry program were reviewed. Demographic characteristics were evaluated (age, gender and weight), CD4 cell count and histopathology - inflammatory activity (A) and fibrosis grade, by METAVIR classification. The significance level adopted was 5%. RESULTS: Eighty one patients were evaluated, 22 treated with IFN+RBV and 59 treated with PEG+RBV. Both were similar relating to age, gender, weight, CD4 cell count and fibrosis grade. Those treated with IFN+RBV presented a greater proportion of A2+A3 patients than those treated with PEG+RBV (P

Introduction: metastatic renal cell carcinoma (mRCC) is highly resistant to chemotherapeutics, rendering limited antitumor effect. Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, may benefit patients with this disease. The Global ARCC Trial (Temsirolimus, Interferon Alfa, or Both for Advanced Renal-Cell Carcinoma) compared temsirolimus alone or temsirolimus plus interferon alfa with interferon alfa alone in mRCC. It has demonstrated that, as compared with interferon alfa, temsirolimus improved overall survival among patients with metastatic renal-cell carcinoma and a poor prognosis while the addition of temsirolimus to interferon did not improve survival. Aim: the objective of our study was to investigate the pharmacoeconomic impact in the Italian context of temsirolimus vs interferon alfa in patients with metastatic renal-cell carcinoma and a poor prognosis. Methods: economic evaluation is based on clinical outcome data from the ARCC trial and was carried out conducting a cost/effectiveness analysis, comparing economic and clinical consequences of temsirolimus (25 mg weekly) vs interferon alfa (18 MU 3 times weekly) in the perspective of the Italian National Health Service. Direct medical costs included in the analysis were drug costs, costs associated with the management of treatment-related serious adverse events (grade 3 and 4), cost related to progression and best supportive care. Effects were measured in terms of overall survival. A sensitivity analysis was performed. Results: the cost of temsirolimus or interferon alfa therapy amounted to approximately € 14,000 and € 2,000 patient respectively. The cost of hospitalization related to drug toxicity was about € 1,500 for temsirolimus and € 2,100 for interferon alfa. Temsirolimus shows an incremental cost per patient per month saved of € 3,767. Sensitivity analysis demonstrates that cost consequences parameters are sensitive to fluctuation. Discussion: this study is the first economic evaluation of ARCC trial based on the Italian context. This evaluation found that temsirolimus therapy in patients with metastatic renal-cell carcinoma and a poor prognosis is cost-effective.

O objetivo do trabalho é descrever o uso de interferon alfa no tratamento de pacientes com hemangioma gigante. Os autores relatam e analisam dois casos de hemangioma gigante em tratamento com interferon alfa. IBS, 3 anos, em acompanhamento no Ambulatório de Hematologia desde um ano de idade com quadro de lesão angiomatosa em praticamente toda hemiface direita, acompanhada de sangramentos gengivais importantes. Após a realização de exames complementares (Angiorressonância magnética) e feito o diagnóstico de hemangioma gigante em face, foi iniciado tratamento com prednisona e, posteriormente, associação com interferon alfa e observada importante melhora do quadro, resultando na diminuição dos episódios de sangramento e no tamanho do tumor. C.N.P., 12 anos, apresentando nódulo em região lateral de joelho esquerdo há 2 anos, com aumento progressivo do tamanho e dor local. Fez uso de prednisona e, sem melhora do quadro, introduzido interferon alfa com regressão importante do tamanho do tumor. O tratamento com interferon alfa deve ser considerado no tratamento de hemangiomas, pois apresenta bons resultados em relação à diminuição do tamanho do tumor e, conseqüentemente, reduz as intercorrências clínicas associadas à sua presença, principalmente os sangramentos.The aim of this study is to describe the treatment using interferon-alpha of giant hemangiomas in children. The authors report two cases of children presenting with giant hemangiomas treated using interferon-alpha and analyze the results. IBS, 3 years-old, has been followed up in Famema Hemathology Service since she was 1 year-old with a tumor on the face and persistent bleeding. After clinical and radiologic evaluations and suggested the diagnosis of giant hemangioma, she started treatment with interferon-alpha. A great clinical improvement was observed a reducing of the number of episodes of bleedings and a decrease in of the tumor size. CNP, 12 years-old, came to this service in the last year presenting with a small painful tumor on the left knee. She had already tried a treatment with Prednisone with no improvement. Treatment with interferon-alpha was initiated with a significant decrease in its size. The use of interferon-alpha should be considered in the treatment of giant hemangioma due to its favorable results related to a reduction in the tumor size and the episodes of bleeding.

Nos últimos anos, houve um grande progresso no tratamento da hepatite B crônica. Cinco drogas são hoje aprovadas para tratamento dessa virose: intérferon alfa, lamivudina, adefovir, entecavir e telbivudina. Os intérferons (convencionais ou peguilados) foram as primeiras drogas utilizadas no tratamento dessas infecções podendo levar a resposta sustentada (perda do DNA-VHB e do AgHbe) em até um terço dos casos tratados. Um grande número de análogos de nucleosídeos/nucleotídeos estão no momento, disponíveis para tratar a hepatite B; a eficácia da lamivudina, o primeiro análogo de nucleosídeo utilizado, é limitada pela elevada incidência de resistência. O adefovir tem eficácia comparável à lamivudina porém baixa freqüência de resistência. Entecavir e tenofovir também se mostram muito ativos em controlar a replicação do vírus da hepatite B, e estão associados com mínimo desenvolvimento de resistência, mesmo em tratamento prolongados. Outras drogas, tais como telbivudina, emtricitabina e clevudine, se tornarão em futuro próximo, novas armas no controle dessa virose. Co-infectados HIV/VHB representam um grupo de doentes de difícil manuseio e que hoje se beneficiam com combinações de drogas no esquema anti-retroviral potente que devem atuar em ambas as viroses. O desenvolvimento de antivirais mais potentes e novas associações de medicamentos, conjuntamente com a melhor compreensão dos mecanismos de resistência do vírus da hepatite B a terapia são importantes conquistas para melhorar a eficácia do tratamento e diminuir no futuro, a carga global de portadores do vírus da hepatite B.Over the last years there has been considerable progress in the treatment of chronic hepatitis B. Five drugs are now approved for the treatment of this virosis: interferon alpha, lamivudine, adefovir, entecavir and telbivudine. Interferons (conventional or PEG) were the first medicine used in the treatment of hepatitis being able to lead the persistent response (loss of DNA-HBV and of AgHbe) to up to one third of treated cases. A large number of nucleoside/nucleotide analogues are, at present, available to treat hepatitis B. The efficacy of lamivudine, the first nucleoside analogue used, is limited by the high rate of resistance. Adefovir has efficacy comparable to that of lamivudine, but with low resistance rate. Entecavir and tenofovir have also been particularly active in the control of hepatitis B virus replication and are associated with minimal resistance development, even during long treatment regimens. Other drugs, such as telbivudine, emtricitabine and clevudine, will become new treatment options in the near future. Individuals co-infected with HIV/HBV are particularly difficult to manage and are nowadays able to benefit from combinations of drugs of the HAART therapy, which should be effective towards both viruses. The development of more potent antiviral drugs as well as new drug combinations, together with a better understanding of hepatitis B virus resistance mechanisms are important milestones to improve treatment efficacy and to diminish, in the future, the global burden of hepatitis B virus.

Introduction: We evaluated the antiviral activities of ribavirin (RBV) and interferon (IFN) alfa as monotherapy and combination therapy against chikungunya virus (CHIKV).Methods: Vero cells were infected with CHIKV in the presence of RBV and/or IFN alfa, and viral production was quantified by plaque assay. A mathematical model was fit to the data to identify drug interactions for effect. We ran simulations using the best-fit model parameters to predict the antiviral activity associated with clinically relevant regimens of RBV and IFN alfa as combination therapy. The model predictions were validated using the hollow fiber infection model (HFIM) system.Results: RBV and IFN alfa were effective against CHIKV as monotherapy at supraphysiological concentrations. However, RBV and IFN alfa were highly synergistic for antiviral effect when administered as combination therapy. Simulations with our mathematical model predicted that a standard clinical regimen of RBV plus IFN alfa would inhibit CHIKV burden by 2.5 log10 following 24 hours of treatment. In the HFIM system, RBV plus IFN alfa at clinical exposures resulted in a 2.1-log10 decrease in the CHIKV burden following 24 hours of therapy. These findings validate the prediction made by the mathematical model.Conclusions: These studies illustrate the promise of RBV plus IFN alfa as a potential therapeutic strategy for the treatment of CHIKV infections. [ABSTRACT FROM AUTHOR]

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Se realizó un estudio prospectivo de los donantes habituales de sangre de los bancos municipales de 10 de Octubre y Guanabacoa durante el año 1999, donde se encontraron 50 pacientes con el antígeno C positivo para la hepatitis. Estos pacientes fueron remitidos a nuestro hospital, donde se confeccionó historia clínica completa, se realizaron las pruebas funcionales hepáticas, ultrasonido, laparoscopia con biopsia y se trataron con interferón. Se observó que el 100 % eran asintomáticos, un 30 % mostró ligero aumento de la TGP. El 80 % presentó hepatomegalia detectable en el ultrasonido. Al realizarles la histopatología, el 72 % poseía una hepatitis crónica. El 60 % de la muestra recibió tratamiento con interferón alfa mostrando negativización del antígeno C de la hepatitis, pero a pesar de esto continuaron evolucionando a la cronicidad.A prospective study of the habitual blood donors from the municipal blood banks of 10 de Octubre and Guanabacoa municipalities during 1999 was conducted. 50 patients with positive hepatitis C antigen were found. These patients were referred to our hospital, where complete medical histories were taken. They underwent hepatic function test, ultrasound, laparoscopy with biopsy and they were treated with interferon. It was observed that 100 % were asymptomatic. 30 % showed a mild increase of TGP. 80 % presented hepatomegaly detectable in the ultrasound. On performing the histopathology, 72 % had chronic hepatitis. 60 % of the sample received treatment with interferon alpha and their response to hepatitis C virus antigen was negative. However, they continue evolving to chronicity.

Objective: Combination of interferon (IFN) alfa and ribavirin therapy is widely used for the treatment of chronic hepatitis C. Various side effects such as flu like symptoms, depression, autoimmune tiroiditis, vertigo, skin rashs, acute myocarditis and bone marrow supression may be seen with this therapy, however, the effect on hearing levels is not clearly evaluated. In this study, we investigated the effect of IFN alfa-2b and ribavirin combination therapy on the hearing levels in patients with chronic hepatitis C. Material and Method: Nineteen patients, who diagnosed as chronic hepatitis C and performed audiogram were included the study. Diagnosis was made by HCV-RNA positivity and liver biopsy. Combination of IFN alfa-2b (3 MÜ, 3 days in a week, sc) and ribavirin (1000-1200 mg/day, po) was given to patiens for 12 months. Audiograms were performed to patiens before and 3rd, 6th, 12,h months during the therapy and 6lh months after the therapy. In audiograms, pure tone average and speech thresholds values were measured as decibels; in addition, speech discrimination rate was detected (speech discrimination-SD, %). Paired t test was used for the statistical analysis. Results: Eleven of patiens were men and 8 of them were women. Mean age was 50.1 years (21-68 years). No significant differences were found in pure tone average, speech thresholds values and speech discrimination rates on audiogram of patients, before and 3rd, 6th, 12th months during the therapy and 6"' months after the therapy (p>0.05). Conclusion: Combination of IFN alfa-2b and ribavirin therapy does not effect the healing levels in patients with chronic hepatitis C. [ABSTRACT FROM AUTHOR]

This paper provides characteristics of extrahepatic manifestations of HBV (hepatitis B virus) infection. Their clinical symptomatology may be extremely rich including glomerulonephritis, polyarteritis nodosa, mixed cryoglobulinemia, peripheral neuropathies and other. Various regimens of treatment of these disorders were proposed and efficacy of IFN alpha in children suffering from glomerulonephritis has been stressed. [ABSTRACT FROM AUTHOR]

Objective To ascertain whether the current practice at Auckland City Hospital of adding interferon to BCG in patients with high risk or recurrent non-muscle invasive bladder cancer ( NMIBC) unable or unwilling to undergo radical cystectomy is effective. Subjects and Method This study examined all institutional cases where BCG alone had not been effective or tolerated as primary treatment for NMIBC and the next guideline agreed step of radical cystectomy was unable to be performed. We identified all patients unwilling or unable to undergo radical cystectomy due to patient co-morbidities or preference for whom ongoing treatment and care was required and included 45 in the data analysis. Current practice at Auckland City Hospital is adding interferon α-2b to BCG for this population group and all patients that were given this therapy with at least three years of follow up data from diagnosis were included into the study. Patients were either on maintenance BCG or single dosing. Several secondary outcomes were also assessed concurrently to the primary objective. Results This observational study showed that adding interferon to BCG proved to be an effective therapy for both treatment and salvage therapy in this patient group with 56% of the patients disease (and recurrence) free at the time of audit. 8/45 patients died whilst undergoing treatment with two of these as a direct result of bladder cancer due to disease progression. Conclusion This therapy has improved outcomes at our institution and has a place as a treatment of choice in this difficult to manage patient group. [ABSTRACT FROM AUTHOR]

Background. The role of natural killer (NK) cells in the process of hepatitis B virus (HBV) surface antigen (HBsAg) clearance and whether their phenotype is related to treatment outcome in patients with chronic hepatitis B are currently unknown. Methods. Patients with chronic hepatitis B (HBV DNA load, >17 000 IU/mL) were treated with pegylated interferon alfa-2a and adefovir for 48 weeks. NK cell phenotype and function were analyzed in 7 responders (defined as individuals with HBsAg clearance by week 72; 3 HBV e antigen [HBeAg]-positive and 4 HBeAg-negative), 7 matched nonresponders, and 7 healthy controls. Subsequently, 34 baseline samples from HBeAg-positive patients with chronic hepatitis B were analyzed. Results. During treatment, the percentage and absolute number of CD56bright NK cells increased significantly, whereas the percentage and absolute number of CD56dim NK cells decreased. At baseline, responders had a significantly lower expression of chemokine receptor CX3CR1 on CD56bright NK cells and inhibitory receptor NKG2A on CD56dim NK cells, compared with nonresponders. In addition, responders had higher CD56bright TRAIL expression and interferon γ production at end of treatment. These baseline differences were not found in HBeAg-positive patients who had HBeAg seroconversion without HBsAg clearance. Conclusions. Combination therapy significantly influences NK cell phenotype and function. Differences between patients with chronic hepatitis B with HBsAg clearance and nonresponders suggest that NK cells play a role in the clearance of HBsAg during interferon-based combination therapy. [ABSTRACT FROM AUTHOR]

Cryoglobulinemia is a systemic disorder in which the blood contains inmunoglobulins that reversibly precipitate in the cold, giving rise to immune complex deposition that may cause small vessel vasculitis. A strong association with Hepatitis C has been made in the latest years. We describe a patient with hepatitis C and Cryoglobulinemia who wazzu developed one of the most severe crises with clinical manifestations of gangrene in feet and upper extremities. Patient ended with amputation of the lower limbs. His life was saved with plasmapheresis, use of frozen plasma, steroids, heparin and alfa interferon. In this article we report the case and we do a review of the literature on cryoglobulinemia. (Rev Med Hered 1997;8:183-188).

Introduction: Chronic hepatitis C is a disease with a high prevalence in the population of intravenous drug users. Serious clinical course of the disease, which can lead to cirrhosis of the liver with all its complications, has a large epidemiological and clinical significance. This study was aimed at assessing the success of antiviral treatment of chronic hepatitis C in intravenous drug users and defining indicators of successful treatment in this population. Materials and Methods. This retrospective study included 316 patients treated with standard therapy for chronic hepatitis C, pegylated interferon and ribavirin, at the Department of Infectious Diseases, Clinical Center of Vojvodina in Novi Sad in the period from January 2007 to December 2012. The patients were divided into a group of intravenous drug users (n = 163) and a group of other modes of transmission of hepatitis C virus (n = 153). The indicators of successful treatment were measured in both groups. Results. A total 51.57% of the subjects belonged to the group of intravenous drug users. The therapy was successful in 87.15% of cases, while the success was achieved in only 53.47% of cases in the group of patients infected otherwise. The positive effect of therapy was associated with younger age, shorter duration of infection, low levels of fibrosis and a higher percentage of infected with hepatitis C virus genotypes 2 and 3. Conclusion. The population of intravenous drug users can be effectively treated with the standard therapy for chronic hepatitis C, even more successfully than the population infected in some other way. [ABSTRACT FROM AUTHOR]

There are no well established treatment guidelines about acute hepatitis C (AHC), leaving physicians to make several challenging decisions, such whether to treat, when to treat and what treatment regimens to use. This article examines the diagnosis of acute infection and critically appraises the various treatment regimens.

Hepatitis C virus (HCV) is the principal cause of hepatic pathology. The usual treatment for chronic HCV infection is the combination of alpha pegylated interferon and ribavirine. The psychiatric adverse effects associated to this treatment are: anxiety, depression, mania, delirium and psychosis (although this one is less common). Patients with severe mental illness, with or without substance abuse problems, display virological responses to the treatment for HCV infection similar to general population. There are not definitive data to support that these patients can not be treated or even re-treated although the initial treatment had not been effective or if they had suffered psychotic decompensations attributable to it. However it is recommended to hospitalize the patient to have a tighter control. Patients with chronic psychosis diagnosis must not be excluded if they are psychopatological stable, they do psychiatric monitoring regularly, they have good treatment adherence and they live in a supportive environment. The decision must be made individually. The treatment of psychiatric symptoms produced by alpha interpheron and ribavirine consists in stopping antiviral treatment and introducing antipsychotic medication. In most cases, the symptoms are reduced, although several resistant cases have been described. [ABSTRACT FROM AUTHOR]

Background & Aims: Interferon treatment for chronic hepatitis C is associated with non-specific symptoms including fever. We aimed to determine the association of temperature changes with interferon antiviral activity. Methods: 60 treatment-naïve patients with chronic hepatitis C (67% genotype 1/4/6, 33% genotype 2/3) were admitted to start peginterferon alfa-2a and ribavirin in a clinical trial. Temperature was measured at baseline and 3 times daily for the first 24h and the maximal increase from baseline during that time (ΔTmax) was determined. Serum HCV-RNA, interferon-gamma-inducible protein-10 (IP-10) and expression of interferon-stimulated genes (ISGs – CD274, ISG15, RSAD2, IRF7, CXCL10) in peripheral blood mononuclear cells (PBMCs) were measured at very early time points, and response kinetics calculated. The IL28B single nucleotide polymorphism, rs12979860, was genotyped. Results: Temperatures rose by 1.2±0.8°C, peaking after 12.5h. ΔTmax was strongly associated with 1st phase virological decline (r=0.59, p <0.0001) and was independent of gender, cirrhosis, viral genotype or baseline HCV-RNA. The association with 1st phase decline was seen in patients with rs12989760CC genotype (r=0.65, p <0.0001) but not in CC/CT (r=0.13, p =0.53) and patients with CC genotype had a higher ΔTmax (1.4±0.8°C vs. 0.8±0.6°C, p =0.001). ΔTmax was associated with 6- and 24-h induction of serum IP-10 and of PBMC ISG expression, but only in patients with rs12989760CC. ΔTmax weakly predicted early virological response (AUC=0.68, CI 0.49–0.88). Conclusions: Temperature rise following peginterferon injection is closely associated with virological response and is modulated by IL28B polymorphism, reflecting host interferon-responsiveness. [ABSTRACT FROM AUTHOR]

Highlights: [•] Interferon alfa (IFN-α) and ribavirin for chronic hepatitis C achieve limited virological response. [•] The efficacy of adding statins to IFN-α and ribavirin was examined. [•] The addition of statins enhances sustained virological response. [•] The addition of statins does not increase adverse events and withdrawals. [•] Statins may be used as an adjuvant to IFN-α and ribavirin therapy for chronic hepatitis C. [Copyright &y& Elsevier]

Maintenance treatment is used in patients if a curative therapy is not available and is currently explored where curation rates need to be improved in aggressive lymphoma. A discussion of valid endpoints is specifically important in the case of indolent lymphoma. The most valid endpoint for maintenance treatment is clearly overall survival, but adequate trial designs may be difficult to achieve and times to relevant results may be excessive. Therefore other endpoints such as quality-adjusted life year or the time to resistance to maintenance treatment or to resistance to repeated reinduction therapies are explored. Several drugs are used for maintenance treatment. The best data exist for interferon alfa and Rituximab. Interferon alfa is able to prolong survival in indolent lymphoma, but it has too many side effects. Rituximab had proven efficacy in second remission in follicular lymphoma and may be useful even in first remission. It has also proven effective in mantle-cell, marginal, and small lymphocytic lymphoma. Maintenance strategies for chronic lymphocytic leukemia have only been explored in phase II designs so far. However, a number of trials currently explore the use of Rituximab or Lenalidomide in a randomized fashion for chronic lymphocytic leukemia maintenance. At all entities included in the overview, several maintenance treatment trials are under way and patients are to be entered in these trials. [ABSTRACT FROM AUTHOR]

Background: The prophylactic effect of postoperative interferon on recurrence and distant metastasis in stage II or III renal cell carcinoma is unclear. In most studies, interferon has been administered for 6 months or less. Therefore, we performed a clinical study of the efficacy of 1-year postoperative administration of natural interferon α, which is generally used in Japan. Methods: The subjects were patients diagnosed with stage II or III renal cell carcinoma who underwent radical nephrectomy. The subjects were randomly allocated to receive an intramuscular injection of natural interferon α (3 million to 6 million units) 3 times a week for 1 year or to receive follow-up observation until recurrence or metastasis occurred. Chest and abdominal CT were performed once yearly for all patients. The primary endpoint was progression-free survival. Results: From September 2001 to August 2006, a total of 107 patients were registered, but 7 subsequently withdrew from the study. Therefore, 100 patients were included in the analysis. The primary endpoint of progression-free survival did not differ significantly between the groups that received natural interferon α or follow-up observation ( p = 0.456, log-rank test). However, peak hazards of progression in the interferon group were delayed for about 6-10 months compared with the observation group. Conclusion: Progression-free survival showed no improvement after administration of natural interferon α to patients with stage II or III renal cell carcinoma for 1 year after radical nephrectomy. The peak hazards of progression might be delayed by about 6 months by interferon administration. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this review was to examine the toxicity profile of adjuvant interferon (IFN) alfa-2b in melanoma patients from a nursing perspective and to summarize practical information to guide the effective management of common IFN toxicities to improve patient comfort. Methods: This is a narrative summary of both research and review articles identified by searching PubMed, National Cancer Institute, and American Cancer Society websites. It also assesses recognized guidelines on the management of adjuvant IFN toxicity relevant to nurses who are caring for patients receiving adjuvant IFN therapy. Results: Adjuvant high-dose IFN alfa-2b (HDI) as compared with observation significantly prolongs relapse-free survival in patients with melanoma at high risk for recurrence after surgical resection; however, treatment compliance and patient quality of life can be compromised by its toxicity profile. HDI toxicities affect a number of organ systems and the majority of patients will experience some side effects. Common toxicities such as flu-like symptoms, fatigue, anorexia, neuropsychiatric symptoms, and laboratory abnormalities are discussed, along with both pharmacological and nonpharmacological management strategies. Conclusions: The considerable side effects of HDI can be managed using established strategies. Oncology nurses play a significant role in the management of patients with melanoma receiving adjuvant HDI, and their prompt recognition of side effects, together with an understanding of effective pharmacological and nonpharmacological interventions, will improve patient comfort; this has the potential to positively influence treatment adherence and completion of the recommended treatment course. [ABSTRACT FROM AUTHOR]